Standard- or high-dose oxytocin for nulliparous women with confirmed delay in labour: quantitative and qualitative results from a pilot randomised controlled trial.

OBJECTIVE: Evidence suggests that a high dose of oxytocin for nulliparous women at 37-42 weeks of gestation with confirmed delay in labour increases spontaneous vaginal birth. We undertook a pilot study to test the feasibility of this treatment. DESIGN: Pilot double-blind randomised controlled trial. SETTING: Three teaching hospitals in the UK. POPULATION: A total of 94 consenting nulliparous women at term with confirmed delay in labour were recruited, and 18 were interviewed. METHODS: Women were assigned to either a standard (2 mU/min, increasing every 30 minutes to 32 mU/minute) or a high-dose regimen (4 mU/minute, increasing every 30 minutes to 64 mU/minutes) oxytocin by computer-generated randomisation. Simple descriptive statistics were used, as the sample size was insufficient to evaluate clinical outcomes. The constant comparative method was used to analyse the interviews. MAIN OUTCOMES MEASURES: The main outcome measures: number of women eligible; maternal and neonatal birth; safety; maternal psychological outcomes and experiences; health-related quality of life outcomes using validated tools and data on health service resource use; incidence of suspected delay of labour (cervical dilatation of <2 cm after 4 hours, once labour is established); and incidence of confirmed delay of labour (progress of <1 cm on repeat vaginal examination after a period of 2 hours). RESULTS: We successfully developed systems to recruit eligible women in labour and to collect data. Rates of spontaneous vaginal birth (10/47 versus 12/47, RR 1.2, 95% CI 0.6-2.5) and caesarean section (15/47 versus 17/47, RR 1.1, 95% CI 0.6-2.0) were increased, and rates of instrumental birth were reduced (21/47 versus 17/47, RR 0.8, 95% CI 0.5-1.3). No evidence of increased harm for either mother or baby was found. The incidences of suspected delay (14%) and confirmed delay (11%) in labour were less than anticipated. Of those who did not go on to have delayed labour confirmed, all except one woman gave birth vaginally. CONCLUSIONS: A pilot trial assessing the efficacy of high-dose oxytocin was feasible, but uncertainty remains, highlighting the need for a large definitive trial. The implementation of national guidance of suspected and confirmed delay in labour is likely to reduce intervention.

Can mutation and selection explain virulence in human P. falciparum infections?

BACKGROUND: Parasites incur periodic mutations which must ultimately be eliminated to maintain their genetic integrity. METHODS: It is hypothesised that these mutations are eliminated not by the conventional mechanisms of competition between parasites in different hosts but primarily by competition between parasites within the same infection. RESULTS: This process is enhanced by the production of a large number of parasites within individual infections, and this may significantly contribute to parasitic virulence. CONCLUSIONS: Several features of the most virulent human malaria parasite Plasmodium falciparum can usefully be re-interpreted in this light and lend support to this interpretation. More generally, it constitutes a novel explanation for the evolution of virulence in a wider range of microparasites.

The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling.

Recrudescing Plasmodium falciparum parasitaemia is attributed to the switching of PfEMP1, a variant antigen family encoded by the var gene repertoire, and the host's immune response. We have developed a mathematical model which incorporates var gene switching, and variant specific, non-variant specific and non-specific immunity. By conducting a sensitivity analysis of the model we have defined the parameter limits which produce chronic and recrudescing infections. We explore 3 switching mechanisms: ordered, random and uncoupled switching. We show that if var genes switch on and off independently at variable rates through the repertoire a chronic clinical infection is predicted. The fastest switching-on rate that produces a chronic infection is 0.03% per generation. The model predicts that non-variant specific immunity plays an important role in reducing disease severity. This work illustrates the complex relationship between the malaria parasite and its host and shows that var gene switching at rates substantially slower than 2% are essential for parasite survival.

Mutation rates in the dihydrofolate reductase gene of Plasmodium falciparum.

A new method has been established to define the limits on a spontaneous mutation rate for a gene in Plasmodium falciparum. The method combines mathematical modelling and large-scale in vitro culturing and calculates the difference in mutant frequencies at 2 separate time-points. We measured the mutation rate at 2 positions in the dihydrofolate reductase (DHFR) gene of 3D7, a pyrimethamine-sensitive line of P. falciparum. This line was re-cloned and an effectively large population was treated with a selective pyrimethamine concentration of 40 nM. We detected point mutations at codon-46 (TTA to TCA) and codon-108 (AGC to AAC), resulting in serine replacing leucine and asparagine replacing serine respectively in the corresponding gene product. The substitutions caused a decrease in pyrimethamine sensitivity. By mathematical modelling we determined that the mutation rate at a given position in DHFR was low and occurred at less than 2.5 x 10(-9) mutations/DHFR gene/replication. This result has important implications for Plasmodium genetic diversity and antimalarial drug therapy by demonstrating that even with low mutation rates anti-malarial resistance will inevitably arise when mutant alleles are selected under drug pressure.

Cognitive testing with culturally diverse children.

This special section discusses how the psychological status of minority children can be enhanced if psychologists adopt an integrated approach in establishing linkages and in examining interactions and reciprocal effects when assessing ethnically, linguistically, and culturally different children. Implications for conducting culturally relevant assessments of intelligence are discussed. A bioecological model for incorporating these suggested techniques into a program evaluation is suggested.

Bio-ecological approach to cognitive assessment.

Because determining a child's educational program usually takes into consideration the child's cognitive functioning, it is vital that those who are involved in this enterprise recognize that many variables contribute to and explain performance. Thus, careful consideration, assessment, and planning are mandatory to plan a child's individual educational program. This article emphasizes that cognitive assessment is both a formal and an informal process that occurs in several contexts-the school, the home, and the community. Therefore, when psychological evaluators assess the cognitive performance of a child, it is necessary to analyze the complete of his or her social/emotional environments that have contributed to his/her current cognitive performance levels. Thus, it is vital to examine the orientation of family members, the academic assistance students receive at home, as well as the current and previous classroom environments in which the student has been educated. Six nonpsychometric measures (using item equivalency, test-teach-retest, and contextualization) were developed by the authors and are presented in recognition that there are many factors that one must consider when interpreting the performance of a child.

A bio-ecological case study: a Caribbean child.

The present article presents how the bio-ecological assessment system is applied in assessing a child's cognitive intelligence beyond a psychometric intelligence test. The recognition that there are many types of intelligence, such as musical and bodily kinesthetic, is exemplified. The case presented is that of a child with deficient cognitive functioning on the psychometric tests, but advanced functioning on the "Other Intelligence Assessment Measure." Diagnostic impressions are given and implications for report writing and interventions are suggested.